Effect and mechanism of narrow ⁃ band ultraviolet B in promoting vitamin D metabolism and alleviating psoriasis⁃like dermatitis in mice
Author:
Affiliation:
Department of Dermatology,Wuhan First Hospital,Wuhan 430022 ,China
Fund Project:
摘要
|
图/表
|
访问统计
|
参考文献
|
相似文献
|
引证文献
|
资源附件
|
文章评论
摘要:
目的：探讨窄谱中波紫外线（narrow-band ultraviolet B，NB-UVB）通过促进维生素D（vitamin D，VD）代谢缓解咪喹莫特（imiquimod，IMQ）诱导银屑病样小鼠皮炎的效应机制。方法：C57BL/6小鼠背部去毛外涂IMQ乳膏进行银屑病样皮炎的造模，检测小鼠血清中VD代谢产物25（OH）D3和1，25（OH）2D3的含量，以及皮损中VD受体（vitamin D receptor，VDR）mRNA表达；确定NB-UVB照射小鼠的辐照能量后，进行造模联合NB-UVB照射，观察小鼠皮损，检测血清中25（OH）D3和 1，25（OH）2D3的含量、 皮损中VDR和炎症因子[（白细胞介素（interleukin，IL）-17A、IL-23、肿瘤坏死因子（tumor necrosis factor，TNF）-α、IL-1β]的mRNA 表达及蛋白含量及CD3+ CD4+ IL-17A+ T细胞比例。使用特异性抑制剂Dafadine-A阻断小鼠VD代谢关键酶细胞色素P450家族 27 亚家族 A 成员 1（cytochrome P450 family 27 subfamily A member 1，CYP27A1）活性后，再进行造模和 NB-UVB 照射，观察皮损，检测皮损中 CD3+ CD4+ IL-17A+ T 细胞比例、炎症因子表达情况、VDR mRNA 表达情况和血清中 25（OH）D3、1，25（OH）2D3 的含量。结果：银屑病样小鼠模型血清中25（OH）D3、1，25（OH）2D3含量和皮损中VDR的mRNA表达均显著降低。NB-UVB照射银屑病样小鼠模型后，相比模型组，小鼠血清中25（OH）D3、1，25（OH）2D3含量和皮损中VDR的mRNA表达上调，皮损中炎症因子IL-17A、IL-23、TNF-α、IL-1β的表达及含量均下调、CD3+ CD4+ IL-17A+ T细胞比例也显著下降。使用Dafadine-A预处理小鼠后进行造模联合NB-UVB照射，相比IMQ联合NB-UVB照射组，血清中25（OH）D3、1，25（OH）2D3含量和皮损中VDR的mRNA表达均显著降低，皮损中CD3+ CD4+ IL-17A+ T细胞比例和炎症因子IL-17A、IL-23、TNF-α、IL-1β的含量均显著升高。结论：NB-UVB 照射通过促进VD代谢缓解银屑病样小鼠皮肤炎症。特异性阻断VD代谢关键酶CYP27A1活性后，NB-UVB照射缓解银屑病样小鼠皮损及炎症反应的效应显著减弱。
Abstract:
Objective：To investigate the effect and mechanism of narrow-band ultraviolet B（NB-UVB）in promoting vitamin D（VD） metabolism and alleviating imiquimod（IMQ）induced psoriasis -like dermatitis in mice. Methods：C57BL/6 mice were treated with IMQ cream on the back skin to induce psoriasis-like dermatitis. The levels of VD metabolites 25（OH）D3 and 1，25（OH）2D3 in serum were detected，as well as the expression of VD receptor（VDR）mRNA in the skin lesions. After determining the irradiation energy of NB-UVB irradiated mice，the model group combined with NB-UVB irradiation was performed to observe mouse skin lesions. The levels of 25（OH）D3，1，25（OH）2D3 in serum，VDR and inflammatory factors[interleukin（IL）-17A，IL-23，tumor necrosis factor（TNF）-α，IL-1β] mRNA expression and inflammatory factors protein contents in skin lesions，and the proportion of CD3 + CD4 + IL -17A+ T cells were detected. After pretreatment with the specific inhibitor Dafadine - A to block cytochrome P450 family 27 subfamily A member 1 （CYP27A1，a key enzyme in vitamin D metabolism）activity，the mice underwent psoriasiform dermatitis induction followed by NB -UVB irradiation. Skin lesions were observed，the proportion of CD3 + CD4 + IL - 17A+ T cells，inflammatory factors and VDR mRNA expression in the skin lesions，and serum levels of 25（OH）D3 and 1，25（OH）2D3 were detected. Results：The levels of 25（OH）D3 and 1，25（OH）2D3 in the serum of psoriasis - like mouse models and the mRNA expression of VDR in skin lesions were significantly reduced. After NB-UVB irradiation on psoriasis-like mouse model，compared to the model group，the levels of 25（OH）D3，1，25（OH）2D3 in the serum of the irradiated mice and the mRNA expression of VDR in the skin lesions were upregulated. The mRNA expression and content of inflammatory factors IL -17A，IL -23，TNF - α and IL -1β in the skin lesions were downregulated，and the proportion of CD3 + CD4 + IL -17A+ T cells was significantly reduced. Compared to the IMQ+NB -UVB group，Dafadine -A pretreated mice showed significantly decreased serum levels of 25（OH）D3 and 1，25（OH）2D3，reduced VDR mRNA expression in skin lesions，along with significantly increased proportions of CD3+ CD4+ IL-17A+ T cells and elevated inflammatory cytokine levels of IL-17A，IL-23，TNF-α and IL -1β in lesions. Conclusion：NB UVB irradiation ameliorates psoriasiform dermatitis and cutaneous inflammation in mice by promoting VD metabolism. Importantly，specific inhibition of CYP27A1 markedly attenuates the therapeutic effects of NB-UVB on both psoriatic skin lesions and associated inflammatory responses.
